The overall results from this study showed that antiviral treatment, either interferon α‐2b or peginterferon α‐2b combined with ribavirin, is cost effective for patients with mild chronic hepatitis C. This suggests that in general, the most cost effective strategy is to treat patients at a mild stage rather than follow current recommendations and wait and only treat those patients who progress to moderate disease.11,12,13,14
There were however some differences in cost effectiveness according to the subgroup of patients under consideration.
The main results are presented for patients aged 40 years at treatment, the mean age of patients entering the UK mild hepatitis C RCT. For these patients with genotype non‐1 (2 or 3), providing either
interferon α‐2b or peginterferon α‐2b combined with ribavirin at a mild rather than a moderate stage was highly cost effective. For patients aged 40 years with genotype 1, providing either antiviral treatment at a mild rather than a moderate stage was associated with a smaller gain in QALYS and higher additional costs. However, even for patients with genotype 1 the costs per QALY gained from antiviral treatment at a mild stage were below the £30
000) per QALY threshold that has been used to decide whether a new intervention is worthwhile.34
Subgroup analysis showed that for older patients (aged
65 years) with genotype 1, the intervention is unlikely to be cost effective as their remaining life expectancy is insufficient to gain enough QALYS from successful treatment. Conversely, for younger patients (aged
40 years) with mild chronic hepatitis C, antiviral therapy for mild hepatitis C leads to sufficient gain in QALYS, even for patients with genotype 1, to be cost effective. The analysis did not use age adjusted SVRs. There is evidence that SVRs decline with age,6
and incorporating this effect would make antiviral therapy for mild hepatitis C appear even more cost effective for younger rather than older patients.
Our results differ from those of previous studies that have found that antiviral therapy is universally cost effective for patients with chronic hepatitis C.8,9,10,15,17,18
Previous studies did not focus on patients with mild chronic hepatitis C and used SVRs from multinational clinical trials designed to assess safety and efficacy rather than effectiveness.8,9,10,15,17,18
This study improved on previous cost effectiveness models by using empirical data on effectiveness, health service costs, HRQOL, and disease transition. The use of these empirical estimates together with sensitivity analyses that fully tested for uncertainty in the input parameters enabled the model to produce relatively robust estimates of cost effectiveness. While some of the parameters were collected as part of the UK mild hepatitis C RCT and related directly to the provision of antiviral therapy in the UK, the model structure would be transferable to other health care systems. Indeed, the sensitivity analysis also suggested that the results were robust to some of the methodological standpoints taken, in particular the choice of efficacy data. The results have been presented in a transparent way, with separate results presented according to genotype and age, to assist with the transferability of the results to other countries.
For the cost effectiveness analysis of peginterferon α and ribavirin, the model required data on the proportion of patients having an SVR. For this parameter the only data available were from multinational clinical trials of safety and efficacy,6,7
which were adapted, using the effectiveness data from the UK mild hepatitis C RCT, to estimate the effectiveness of peginterferon α‐2b and ribavirin in routine clinical practice. Using the SVRs from this study leads to a conservative estimate of the relative cost effectiveness of providing peginterferon α‐2b and ribavirin at a mild rather than a moderate stage. Recent trial results have shown that the efficacy of peginterferon α‐2a and ribavirin is similar to that for peginterferon α‐2b with ribavirin.36
The general conclusion that peginterferon α‐2b and ribavirin is cost effective for mild hepatitis therefore also applies to peginterferon α‐2a and ribavirin.
Although the findings from this study suggest that providing either antiviral treatment at a mild stage is more cost effective than waiting and only treating those cases who progress to moderate disease, it is less clear whether the additional costs of providing peginterferon α rather than interferon α at a mild stage are justified. The relative cost effectiveness of providing peginterferon α and ribavirin at a mild stage depends on the ceiling ratio used to determine whether or not an intervention is cost effective. It is cost effective to provide peginterferon α rather than interferon α with ribavirin for mild hepatitis C if the ceiling ratio exceeds £33
000) per QALY gained. Providing either
interferon α or peginterferon α with ribavirin for all patients with mild hepatitis C would avoid the need to use a liver biopsy to establish the patient's disease stage. Liver biopsies are costly, invasive, and have a small risk of morbidity and mortality.37
The finding that antiviral therapy is cost effective for patients with genotype 1 relies on HRQOL improving following an SVR. This improvement was only measured in the UK mild hepatitis C RCT over 6–12 months, on a relatively small number of patients. The sensitivity analysis suggested that provided there was any improvement in HRQOL at all following an SVR, then the intervention would be cost effective for patients with genotype non‐1. However, previous studies that have recruited more patients and followed them for longer suggest that the improvement in HRQOL may be greater than that observed in this trial.38,39
The cost effectiveness estimates as presented are therefore likely to be conservative.
The main purpose of this study was to estimate whether antiviral therapy was cost effective for patients with mild hepatitis C who met the eligibility criteria for patients included in the UK mild hepatitis C RCT.20
Certain groups were excluded from the study, including patients with human immunodeficiency virus coinfection, ongoing psychiatric morbidity, intravenous drug use, excessive alcohol intake (>28 units for men and >21 units for women), cardiovascular disease, uncontrolled diabetes mellitus, or haemophilia. The choice of parameter estimates in the model reflects this study's target population. In particular, the decision to use general all cause death rates rather than applying a higher all cause death rate for patients with hepatitis C was based on excluding these patient groups.
In the base case analysis, data from the UK tertiary referral centre that assigned most patients to the RCT were used to estimate transition probabilities. The sensitivity analysis suggested that when transition probabilities were taken from the Trent cohort, which may be more representative of disease progression in the UK, the conclusions were unchanged for patients with genotype non‐1. However, for patients with genotype 1 using these lower disease transition probabilities meant that the cost per QALY gained exceeded £30
000) per QALY. Hence caution should be exercised before applying the findings from the cost effectiveness model to patient groups excluded from the study. Other estimates used in the model, in particular the SVRs following antiviral treatment, may also change if the target population is broadened to include a wider range of patients and centres. Further research is required to establish whether antiviral therapy is effective and cost effective for more general populations of patients with chronic hepatitis C.
To conclude, for patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate stage, and liver biopsies prior to treatment may no longer be justified. Antiviral treatment at a mild rather than a moderate stage is more cost effective for patients with genotype non‐1 than for patients with genotype 1. For patients with genotype 1, the conclusion that antiviral treatment at a mild stage is cost effective depends on the transition probabilities used, the gain in HRQOL following an SVR, and the patient's age. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective. The cost effectiveness of treating mild hepatitis C with peginterferon α rather than interferon α in combination with ribavirin depends on the threshold willingness to pay for a QALY gained.